Auto-Injector with a Torsion Spring

ABSTRACT

The invention relates to an auto-injector for administering a dose of a liquid medicament (M), comprising:
         an elongate housing arranged to contain a syringe with a hollow needle and a bung for sealing the syringe and displacing the medicament (M), the elongate housing having a distal end (D) and a proximal end (P) with an orifice intended to be applied against an injection site, wherein the syringe is slidably arranged with respect to the housing,   spring means capable of, upon activation, pushing the needle from a covered position inside the housing into an advanced position through the orifice and past the proximal end (P) as well as operating the syringe to supply the dose of medicament (M),   activating means arranged to lock the spring means in a pressurized state prior to manual operation and capable of, upon manual operation, releasing the spring means for injection.       

     The spring means is a torsion spring grounded at one end in the housing and at the other end in a first gear member rotatable about a longitudinal axis but axially fixed wherein the first gear member, upon rotation, is arranged for translatively moving a second gear member, the second gear member prevented from rotating and coupled to the bung in order to push it towards the proximal end (P), wherein the first gear member is engaged with the activating means prior to manual operation in a manner to prevent rotation and disengaged from the activating means upon manual operation.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Phase Application pursuant to35 U.S.C. §371 of International Application No. PCT/EP2011/052297 filedFeb. 16, 2011, which claims priority to U.S. Provisional PatentApplication No. 61/412,080 filed on Nov. 10, 2010 and European PatentApplication No. 10153985.6 filed Feb. 18, 2010. The entire disclosurecontents of these applications are herewith incorporated by referenceinto the present application.

FIELD OF INVENTION

The invention relates to an auto-injector for administering a dose of aliquid medicament.

BACKGROUND

Administering an injection is a process which presents a number of risksand challenges for users and healthcare professionals, both mental andphysical.

Injection devices (i.e. devices capable of delivering medicaments from amedication container) typically fall into two categories—manual devicesand auto-injectors.

In a manual device—the user must provide the mechanical energy to drivethe fluid through the needle. This is typically done by some form ofbutton/plunger that has to be continuously pressed by the user duringthe injection. There are numerous disadvantages to the user from thisapproach. If the user stops pressing the button/plunger then theinjection will also stop. This means that the user can deliver anunderdose if the device is not used properly (i.e. the plunger is notfully pressed to its end position). Injection forces may be too high forthe user, in particular if the patient is elderly or has dexterityproblems.

The extension of the button/plunger may be too great. Thus it can beinconvenient for the user to reach a fully extended button. Thecombination of injection force and button extension can causetrembling/shaking of the hand which in turn increases discomfort as theinserted needle moves.

Auto-injector devices aim to make self-administration of injectedtherapies easier for patients. Current therapies delivered by means ofself-administered injections include drugs for diabetes (both insulinand newer GLP-1 class drugs), migraine, hormone therapies,anticoagulants etc.

Auto-injectors are devices which completely or partially replaceactivities involved in parenteral drug delivery from standard syringes.These activities may include removal of a protective syringe cap,insertion of a needle into a patient's skin, injection of themedicament, removal of the needle, shielding of the needle andpreventing reuse of the device. This overcomes many of the disadvantagesof manual devices. Injection forces/button extension, hand-shaking andthe likelihood of delivering an incomplete dose are reduced. Triggeringmay be performed by numerous means, for example a trigger button or theaction of the needle reaching its injection depth. In some devices theenergy to deliver the fluid is provided by a spring.

US 2002/0095120 A1 discloses an automatic injection device whichautomatically injects a pre-measured quantity of fluid medicine when atension spring is released. The tension spring moves an ampoule and theinjection needle from a storage position to a deployed position when itis released. The content of the ampoule is thereafter expelled by thetension spring forcing a piston forward inside the ampoule. After thefluid medicine has been injected, torsion stored in the tension springis released and the injection needle is automatically retracted back toits original storage position.

US 2006/287630 A1 discloses an injection device including a torsionspring with a mid-axis and an output element with a longitudinal axiswhich can be displaced along its longitudinal axis by the torsionspring, the mid-axis of the torsion spring being generally parallel withthe longitudinal axis of the output element.

WO 2009/037141 A1 discloses an injection device comprising a housing, acontainer holder arranged within said housing having a container adaptedto contain medicament to be delivered through a needle, plunger drivemeans, an energy accumulating member adapted to accumulate and transferenergy to said plunger drive means wherein said device further comprisescontainer driver means arranged and designed to be connected to theplunger drive means and to the container holder for holding thecontainer and its needle stationary within said housing before saidenergy is provided to the drive means and for urging the containertowards the proximal end of the device when said energy is provided tothe drive means whereby a needle penetration and respectively aninjection are performed.

WO 2009/098502 A2 discloses an autoinjector device comprising a drivehousing and a syringe housing which can be disconnected to allowinsertion of a syringe. A drive mechanism in the drive housing is cockedby means of a cord connected between the drive housing and the syringehousing. The drive mechanism comprises a drive gear rotatably mounted inthe drive housing and acting as a rotary crank connected by a connectingrod to a plunger. In use the drive gear is driven by a torsion spring sothat the drive mechanism extends the syringe from the syringe housingand expels a dose and then retracts the syringe back into the housing. Afiring button releases the drive gear to be driven by the torsion springbut is also engageable as a brake on the rim of the drive gear.

EP 1 728 529 A1 discloses a device for the delivery of predetermineddoses of liquid medicament to a patient, which medicament is intended tobe inhaled by the patient or intended to be injected into the body ofthe patient. The device is adapted to be in a medicament delivery stateand in a medicament non-delivery state. When the device is in amedicament delivery state, said device is adapted to drive a piston intoa cartridge containing the liquid medicament to be delivered, with aforce that is above or equal to a predetermined minimum force value andbelow a predetermined maximum force value. The minimum force value isthe lowest force value needed to deliver the predetermined dose and themaximum force value is the first force value at which it exists a riskof damaging the cartridge or the components of the device.

SUMMARY

It is an object of the present invention to provide an improvedauto-injector. The object is achieved by an auto-injector according toclaim 1.

Preferred embodiments of the invention are given in the dependentclaims.

An auto-injector for administering a dose of a liquid medicamentaccording to the invention comprises:

-   -   an elongate housing arranged to contain a syringe with a hollow        needle and a bung for sealing the syringe and displacing the        medicament, the elongate housing having a distal end and a        proximal end with an orifice intended to be applied against an        injection site, wherein the syringe is slidably arranged with        respect to the housing,    -   spring means capable of, upon activation, pushing the needle        from a covered position inside the housing into an advanced        position through the orifice and past the proximal end as well        as operating the syringe to supply the dose of medicament,    -   activating means arranged to lock the spring means in a        pressurized state prior to manual operation and capable of, upon        manual operation, releasing the spring means for injection.

In the context of this patent application the term proximal refers tothe direction pointing towards the patient during an injection while theterm distal refers to the opposite direction pointing away from thepatient.

According to the invention the spring means is a torsion spring groundedat one end in the housing and at the other end in a first gear memberrotatable about a longitudinal axis but axially fixed. The first gearmember, upon rotation, is arranged for translatively moving a secondgear member. The second gear member is prevented from rotating andcoupled to the bung in order to push it towards the proximal end. Thefirst gear member is engaged with the activating means prior to manualoperation in a manner to prevent rotation and disengaged from theactivating means upon manual operation. The torsion spring is preferablyloaded or wound during manufacturing of the auto-injector. When thetorsion spring is released by operating the activating means the firstgear member starts rotating.

The single torsion spring is used for both, inserting the needle andfully emptying the syringe. A major advantage of the torsion spring isthat force is exerted on the bung and syringe in a smooth manner,whereas a conventional compression spring exhibits a rather abrupt forcedeployment which may spoil a glass syringe or other parts of theauto-injector.

According to the invention an essentially tube-shaped needle shroud isarranged around the syringe in the housing. The needle shroud isslidable between at least a drawn back position with the needle shroudalmost hidden inside the housing and an advanced position with theneedle shroud protruding from the proximal end and covering the hollowneedle in its advanced position. The needle shroud is biased by a secondspring means towards the advanced position and locked in the drawn backposition by a locking means which is releasable by rotary movementtransmitted from the first gear member through a clutch mechanism whichis engaged by the second gear member shortly before the second gearmember is fully advanced during an injection stroke. Hence, once thedose is complete, the second spring means returns the needle shroud overthe needle. This makes the device safer than an equivalent manualinjection with respect to needlestick injuries.

In a particularly preferred embodiment an interlock mechanism isarranged for locking the activating means and preventing it fromaccidental operation. The interlock mechanism may be coupled to theneedle shroud. The interlock mechanism may be releasable by pushing theneedle shroud a small distance into the housing from the needle shroud'sretracted position. Thus, the device cannot be used until the needleshroud is depressed. In normal use this would occur by pushing thedevice against an injection site, i.e. a patient's skin.

The activating means may be a trigger button laterally arranged at thehousing and operable by being pressed transversally with respect to thelongitudinal axis. Conventional auto-injectors have the trigger buttonat their distal end. The advantage of having the trigger button on theside is that the user is less likely to incur an injury should they beconfused as to which end the needle will appear from.

The trigger button may have a locking pin engageable with at least onedog tooth provided on the first gear member for preventing rotationthereof in order to lock the spring means or keep it locked in apressurized state. The dog teeth may be circumferentially arranged atthe first gear member thus allowing for stopping the rotation andconsequently the injection at any point in time by releasing the triggerbutton. The trigger button may therefore be biased by a return spring.

The shroud locking means may have the shape of a bayonet fit between theneedle shroud and an outer rear tube, which is arranged around thetorsion spring. The needle shroud is guided in the housing in a mannerto prevent relative rotation, e.g. by at least one spline engaging arespective slot in the housing. The outer rear tube is coupled to theclutch mechanism and may therefore be rotated by the torsion spring. Thebayonet fit comprises a bayonet pin and a corresponding pin trackarranged between the outer rear tube and the needle shroud. The pin maybe held behind a track shoulder in order to hold the needle shroud inits retracted position. In order to release the needle shroud the outerrear tube is rotated by a small angle thus turning the bayonet pin awayfrom the track shoulder (or vice versa) and into a straight longitudinalpart of the pin track so the compression spring may forward the needleshroud as soon as the auto-injector is removed from the injection site.

The second gear member may be a piston rod having an external lead screwthread. The piston rod may have an axial bore for slidably arranging thepiston rod on a shaft attached to the housing. The axial bore and theshaft may have corresponding non-circular profiles in order to preventrelative rotation, e.g. square profiles or profiles with at least onespline or flat. The shaft may be directly or indirectly attached to thehousing, e.g. by an end cap. However, the shaft has to be securedagainst rotation relative to the housing.

The first gear member may be a lead nut engaged with the external leadscrew thread of the second gear member. The lead nut may have aninternal lead screw thread or a pin guided in the external lead screwthread of the piston rod. Preferably the lead nut is equipped with atleast one ball bearing in order to achieve a low friction contact.

In one embodiment the external lead screw thread may have a variablepitch. Thus, speed and force of the needle insertion and injection ofthe medicament may be adapted to user convenience and to the fact thatthe torque of the torsion spring is highest when it is fully loaded andlowest near the end of the injection stroke. E.g. the pitch of thethread may be adapted to ensure a quick needle insertion and arelatively slow injection of the medicament in order to cause the leastpossible pain for the patient.

The interlock mechanism may comprise respective catches provided on theneedle shroud and the trigger button. The catches may have the shape ofhooks gearing into each other when the needle shroud is in an initialretracted position. As soon as the needle shroud is pushed in a smalldistance from the retracted position the hook shaped catches arelaterally shifted out of engagement and the trigger button may beoperated. In order to allow the needle shroud to be pushed back from theretracted position a small clearance may be provided in the pin trackbehind the track shoulder.

In a preferred embodiment the syringe is arranged in a syringe carrierand supported by the syringe carrier at a proximal end. Supporting thesyringe at its proximal end rather than at its flanges avoids damagingthe syringe under load since the flanges are more fragile, in particularin a glass syringe. The syringe carrier is slidably arranged in theneedle shroud. An abutment is provided in the needle shroud defining amaximum forward position of the syringe carrier. This allows fordefining an injection depth, e.g. for a subcutaneous or intramuscularinjection.

The clutch mechanism for releasing the needle shroud towards the end ofthe injection may comprise a circumferential shoulder arranged on thesecond gear member, e.g. at its distal end, and at least one resilientclutch finger or a number of resilient clutch fingers with respectiveinclined inner surfaces arranged on a distal end of the first gearmember. The shoulder is arranged for increasingly pressing against theinclined surfaces when forwarded thereby flexing the clutch fingersoutward near the end of an injection stroke. The clutch mechanismfurther comprises an inner rear tube arranged around the clutch fingersinside the torsion spring and attached to the outer rear tube at theirdistal ends. The inner rear tube has a number of internal longitudinalsplines for engaging the flexed-out clutch fingers. Prior to beingflexed out by the shoulder the first gear member, i.e. the lead nut andits clutch fingers spin without engaging the longitudinal splines of theinner rear tube. When the clutch fingers are flexed out radially theyengage with the longitudinal splines in the inner rear tube. Thus therotation of the first gear member is forwarded to the bayonet fit so thebayonet pin comes clear of the track shoulder and gets into the straightlongitudinal part of the pin track thus allowing the needle shroud toslide forward when removed from the injection site. The clutch fingersmay have respective external teeth protruding radially outwardly inorder to provide a defined engagement with the longitudinal splines.

In a preferred embodiment the internal longitudinal splines are arrangedin a manner to form a ratchet when engaged with the clutch fingers. Thisallows for continued rotation of the lead nut even after the outer reartube has been rotated and consequently the bayonet pin has hit the sideof the longitudinal part of the pin track so the bung may be furtherforwarded until it bottoms out in the syringe so dead volume is avoided.This is particularly advantageous as it ensures improved dose accuracyand no wastage of expensive medicaments as the syringe or cartridge isfully emptied. By contrast a purely positive locking engagement betweenthe clutch fingers and the longitudinal splines would stall the rotarymovement as soon as the bayonet pin hits the side of the longitudinalpart of the pin track. Furthermore the ratchet style engagement providesan acoustic feedback for the user announcing the upcoming end of theinjection. During this time, e.g. ten seconds the user is asked to keeppressure on the injection site.

As the user withdraws the auto-injector from the injection site afterthe end of injection the needle shroud is pushed over the needle by thecompression spring into its advanced position. A locking mechanism maybe provided for locking the needle shroud in its advanced position sothe needle cannot be re-exposed and needle stick injuries with the nowcontaminated needle are avoided.

The housing may have at least one viewing window for inspecting thesyringe.

The auto-injector may preferably be used for subcutaneous orintra-muscular injection, particularly for delivering one of ananalgetic, an anticoagulant, insulin, an insulin derivate, heparin,Lovenox, a vaccine, a growth hormone, a peptide hormone, a proteine,antibodies and complex carbohydrates.

The term “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, anantibody, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy, wherein in a further embodiment thepharmaceutically active compound comprises at least one human insulin ora human insulin analogue or derivative, glucagon-like peptide (GLP-1) oran analogue or derivative thereof, or exedin-3 or exedin-4 or ananalogue or derivative of exedin-3 or exedin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exedin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus, are not limitiveof the present invention, and wherein:

FIG. 1 is a perspective view of an auto-injector with a needle shroudand a lateral trigger button,

FIG. 2 is a longitudinal section of the auto-injector in a prior to usestate,

FIG. 3 is a perspective detail view of the longitudinal section of FIG.2 with the needle shroud and the trigger button interlocked,

FIG. 4 is a perspective detail view with the trigger button releasedfrom the interlock by pressing the needle shroud against an injectionsite,

FIG. 5 is a perspective detail view with the trigger button pressed,

FIG. 6 is a longitudinal section of the auto-injector with a syringe andan injection needle advanced in order to pierce a patient's skin,

FIG. 7 is a detail view of the longitudinal section of FIG. 6,

FIG. 8 is a longitudinal section of the auto-injector with a piston rodadvancing a bung in order to expel a liquid medicament from the syringe,

FIG. 9 is a detail view of FIG. 8 with a clutch mechanism,

FIG. 10 shows perspective views of two alternative clutch mechanisms,

FIG. 11 is a perspective view of the auto-injector with a bayonet fitbetween the needle shroud and an outer rear tube, the needle shroudprevented from moving forward,

FIG. 12 is a perspective view of the auto-injector with the bayonet fit,the outer rear tube rotated in order to allow the needle shroud to moveforward,

FIG. 13 is a perspective view of the auto-injector with the bayonet fit,the needle shroud pushed forward by means of a bias spring, and

FIG. 14 is a longitudinal section of the auto-injector with the needleshroud fully advanced and locked in forward position in order to protectthe needle.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1 shows a perspective view of an auto-injector 1 with an elongatehousing 2 and a needle shroud 3 for protecting a needle (not shown). Alateral trigger button 4 may be transversally pressed in order totrigger an automatic injection. The trigger button 4 is interlocked withthe needle shroud 3 so it cannot be pressed until the needle shroud 3 ispushed into the housing 2 by placing it on an injection site, e.g. apatient's skin and applying pressure. The needle shroud 3 haslongitudinal splines 5 engaged in corresponding grooves in the housing 1for preventing relative rotation of the needle shroud 3 with respect tothe housing 1. A viewing window 6 allows for viewing and inspecting asyringe held in the auto-injector 1.

FIG. 2 shows a longitudinal section of the auto-injector 1 in a prior touse state. A syringe 7 is partially surrounded and supported at a frontend by a syringe carrier 8. Attached at the front end of the syringe 7is a hollow needle 9 for piercing a patient's skin and delivering aliquid medicament M stored inside the syringe 7. Near the distal end ofthe syringe 7 a bung 10 is arranged for sealing and containing themedicament. The bung 10 may be advanced by a piston rod 11 in order toexpel the medicament M from the syringe 7. The syringe carrier 8 isslidably arranged inside the needle shroud 3. The needle shroud 3 isbiased by a compression spring 12 towards a proximal end P. A bayonetfit (shown in FIG. 11) between the needle shroud 3 and an outer reartube 13 serves for holding the needle shroud 3 in a retracted positionagainst the bias of the compression spring 12 prior to use, thusenabling the patient to grab and remove the rubber needle shield (notshown).

A torsion spring 14 is arranged inside the outer rear tube 13 and withone end attached to a distal end D of the housing 2 so torque from thetorsion spring 14 is reacted into the housing 2. The other end of thetorsion spring 14 is coupled to a lead nut 15 which is rotatably mountedaround the piston rod 11. The piston rod 11 has an external lead screwthread 16 engaged with the lead nut 15. The lead nut 15 is equipped withat least one ball bearing 17 for this engagement. It could alternativelyhave at least one pin. In the prior to use state shown in FIG. 2 thelead nut 15 is biased by the torsion spring 14 but kept from rotating bya locking pin 18 arranged at the trigger button 4 engaged with a dogtooth 19 arranged at the lead nut 15. An inner rear tube 20 is arrangedinside the torsion spring 14 and around the piston rod 11 and part ofthe lead nut 15. The piston rod 11 is guided along a shaft 21 arrangedin an axial bore of the piston rod 11. The axial bore and the shaft 21both have a non-circular profile in order to keep the piston rod 11 fromrotating, e.g. a square profile or a profile with at least one spline orflat. The shaft 21 is attached to an end cap 22 arranged at the distalend D of the auto-injector 1.

A protective needle shield (not shown) may be provided which has to beremoved prior to use by a user resulting in the situation of FIG. 1. Inthis situation the needle 9 is a safe distance back within the needleshroud to protect the user from accidental needlestick injuries.

FIG. 3 shows a perspective detail view of the longitudinal section ofFIG. 2 with the needle shroud 3 and the trigger button 4 interlocked bycatches 24, 25 provided at the needle shroud 3 and the trigger button 4,respectively.

In order to prepare for an injection the user pushes the proximal end Pof the auto-injector 1 against the injection site. Thus the needleshroud 3 is moved into the auto-injector 1 by a small distance bigenough to release the interlocking catches 24, 25 from each other. Thissituation is shown in FIG. 4. The compression spring 12 opposes themotion of the needle shroud 3 but is specified such that its spring rateand preload are low enough to feel natural for the user. The triggerbutton 4 may now be operated.

FIG. 5 shows the distal end of the trigger button 4 being pressed thusrotating the trigger button 4 about a trigger pivot 26 in the housing 2,raising the proximal end of the trigger button 4 and moving the lockingpin 18 out of the engagement with the dog tooth 19 of the lead nut 15.Thus the lead nut 15 is released and torque from the torsion spring 14causes the lead nut 15 to rotate. Since the lead nut 15 abuts against athrust face 27 in the housing 2 it is kept from moving in distaldirection D due to the load applied to the piston rod 11 while rotating.

Instead, as shown in FIG. 6, the piston rod 11, kept from rotating bythe shaft 21, is pushed forward in proximal direction P due to theengagement of the lead nut 15 and the lead screw thread 16. Theadvancing piston rod 11 pushes against the bung 10 which in turnadvances the syringe 7 by virtue of the friction between the bung 10 andthe syringe wall and due to the thin fluid channel inside the hollowneedle 9 opposing the displacement of the medicament M. The advancingsyringe 7 also causes the needle 9 to protrude beyond the proximal end Pof the auto-injector 1 into the injection site, e.g. the patient's skin.Since the syringe 7 is supported at its proximal end by an orifice ofthe syringe carrier 8 the syringe carrier 8 is also advanced with thesyringe 7 until the syringe carrier 8 abuts against an abutment in theneedle shroud 3 as shown in FIG. 6. This contact sets the injectiondepth relative to the needle shroud 3.

FIG. 7 is a detail view of the longitudinal section of FIG. 6.

After the syringe carrier 8 has hit the abutment of the needle shroud 3the syringe 7 is kept from advancing further. With the lead nut 15 stillrotating and pushing the piston rod 11 the bung 10 overcomes thefriction and the hydraulic resistance of the medicament M and advancesinside the syringe 7 thereby displacing the medicament M and deliveringit through the fluid channel of the hollow needle 9 into or through thepatient's skin. This situation is shown in FIG. 8.

FIG. 8 shows the piston rod 11 and the bung 10 almost fully advanced andthe syringe 7 almost entirely emptied but for a small residue. Referringnow to FIGS. 9 and 10 a and 10 b showing different detail views of thecutout marked in FIG. 8, just before the bung 10 bottoms out in thesyringe 7 a shoulder 28 on the distal end of the piston rod 11 behindthe lead screw thread 15 is pushed into clutch fingers 29 on the distalend of the lead nut 15 thereby bending the clutch fingers 29 radiallyoutward. Each clutch finger 29 has an external tooth 30 which nowengages with a respective internal longitudinal spline 31 provided inthe proximal end of the inner rear tube 20, causing the inner rear tube20 to rotate along with the lead nut 15. The splines 31 are arranged ina ratchet manner in FIG. 10 a.

FIG. 10 b shows an alternative embodiment with rounded finger teeth 30.In both embodiments (FIGS. 10 a and 10 b) the clutch mechanism isarranged to let the clutch fingers 29 generate enough torque on thelongitudinal splines 31 to partially rotate the outer rear tube 13 torelease a bayonet fit described below in FIG. 11. However the torquegenerated has to be low enough to let the lead nut 15 continue rotatingwith the spring arms jumping over the splines 31 and making a rattlingnoise indicating that the injection has been nearly finished. The innerrear tube 20 is coupled with the outer rear tube 13 near the distal endD of the auto-injector 1 (cf. FIG. 8). Thus the outer rear tube 13 isalso rotated. The outer tube 13 has a circumferential slot (notillustrated) to allow the distal end of the torsion spring to passthrough to the housing 2 for grounding the torsion spring 14. Thecircumferential slot has to be long enough to allow a partial rotationof the outer rear tube 13 in order to disengage the bayonet fitdescribed below in FIG. 11.

FIG. 11 shows a perspective view of the auto-injector 1 just before theengagement of the clutch fingers 29 with the internal longitudinalsplines 31. The bayonet fit between a pin 32 of the needle shroud 3 anda pin track 33 of the outer rear tube 13 is still in a state with thepin 32 behind a track shoulder 34 so the needle shroud 3 would be heldin position against the bias of the compression spring 12 if the stilldepressed needle shroud 3 was released. A small axial clearance behindthe track shoulder 34 allows the needle shroud 3 to be pushed in distaldirection D just enough to disengage the interlock between the button 4and the needle shroud 3 as described above.

When the clutch fingers 29 are engaged with the internal longitudinalsplines 31 the outer rear tube 13 is rotated so as to disengage thebayonet fit by the pin 32 coming clear of the track shoulder 34 so theneedle shroud 3 may be pushed forward by the compression spring 12 (seeFIG. 12). At this point the user is asked to keep pressure with theauto-injector 1 at the injection site for a short period of time, e.g.ten seconds. During this time the lead nut 15 is still rotating andforwarding the piston rod 11 and bung 10 until the bung 10 bottoms outat the proximal end of the syringe 7 thereby virtually entirelydisplacing the rest of the medicament M from the syringe 7.

As the user withdraws the auto-injector 1 from the injection site theneedle shroud 3 is pushed over the needle 9 in proximal direction P bythe compression spring 12. This situation is shown in FIGS. 13 and 14. Alocking mechanism, such as a unidirectional barb or other known to thoseskilled in the art, may be provided to lock the needle shroud 3 in thisforward position in order to prevent re-exposure of the needle.

The auto-injector 1 may preferably be used for delivering one of ananalgetic, an anticoagulant, insulin, an insulin derivate, heparin,Lovenox, a vaccine, a growth hormone, a peptide hormone, a proteine,antibodies and complex carbohydrates.

1-14. (canceled)
 15. Auto-injector for administering a dose of a liquidmedicament (M), comprising: an elongate housing arranged to contain asyringe with a hollow needle and a bung for sealing the syringe anddisplacing the medicament (M), the elongate housing having a distal end(D) and a proximal end (P) with an orifice intended to be appliedagainst an injection site, wherein the syringe is slidably arranged withrespect to the housing, spring means capable of, upon activation,pushing the needle from a covered position inside the housing into anadvanced position through the orifice and past the proximal end (P) aswell as operating the syringe to supply the dose of medicament (M),activating means arranged to lock the spring means in a pressurizedstate prior to manual operation and capable of, upon manual operation,releasing the spring means for injection, wherein the spring means is atorsion spring grounded at one end in the housing and at the other endin a first gear member rotatable about a longitudinal axis but axiallyfixed, wherein the first gear member, upon rotation, is arranged fortranslatively moving a second gear member, the second gear member beingprevented from rotating relative to the housing and coupled to the bungin order to push it towards the proximal end (P), wherein the first gearmember is engaged with the activating means prior to manual operation ina manner to prevent rotation and disengaged from the activating meansupon manual operation, wherein an essentially tube-shaped needle shroudis arranged around the syringe in the housing, the needle shroudslidable between at least a retracted position with the needle shroudalmost hidden inside the housing and an advanced position with theneedle shroud protruding from the proximal end (P) and covering thehollow needle in its advanced position, wherein the needle shroud isbiased by a second spring means towards the advanced position,characterized in that the needle shroud is locked in the retractedposition by a locking means which is releasable by rotary movementtransmitted from the first gear member through a clutch mechanism whichis engaged by the second gear member shortly before the second gearmember is fully advanced during an injection stroke.
 16. Auto-injectoraccording to claim 15, characterized in that an interlock mechanism isarranged for locking the activating means and preventing it from beingmanually operated, wherein the interlock mechanism is coupled to theneedle shroud, wherein the interlock mechanism is releasable by pushingthe needle shroud a small distance into the housing from the needleshroud's refracted position.
 17. Auto-injector according to claim 15,characterized in that the activating means is a trigger button,laterally arranged at the housing and operable by being pressedtransversally with respect to the longitudinal axis.
 18. Auto-injectoraccording to claim 17, characterized in that the trigger button has alocking pin engageable with at least one dog tooth provided at the firstgear member for preventing rotation thereof in order to lock the springmeans in its pressurized state.
 19. Auto-injector according to claim 15,characterized in that the locking means has the shape of a bayonet fitbetween the needle shroud and an outer rear tube arranged around thetorsion spring, wherein the needle shroud is guided in the housing in amanner to prevent relative rotation and wherein the outer rear tube iscoupled to the clutch mechanism, wherein the bayonet fit comprises abayonet pin arranged at one of the outer rear tube or the needle shroudand a pin track arranged in the other one of the outer rear tube or theneedle shroud.
 20. Auto-injector according to claim 15, characterized inthat the second gear member is a piston rod having an external leadscrew thread, the piston rod having an axial bore for slidably arrangingthe piston rod on a shaft attached to the housing, the axial bore andthe shaft having corresponding non-circular profiles, wherein the firstgear member is a lead nut engaged with the external lead screw thread.21. Auto-injector according to claim 20, characterized in that theexternal lead screw thread has a variable pitch.
 22. Auto-injectoraccording to claim 17, characterized in that the interlock mechanismcomprises respective catches provided at the needle shroud and thetrigger button.
 23. Auto-injector according to claim 15, characterizedin that the syringe is arranged in a syringe carrier and supported bythe syringe carrier at a proximal end, wherein the syringe carrier isslidably arranged in the needle shroud and wherein an abutment isprovided in the needle shroud defining a maximum forward position of thesyringe carrier.
 24. Auto-injector according to claim 15, characterizedin that the clutch mechanism comprises a circumferential shoulderarranged at the second gear member and at least one resilient clutchfinger with a respective inclined inner surface arranged at a distal endof the first gear member, the shoulder arranged for increasinglypressing against the inclined surface thereby flexing the clutch fingersoutward near the end of an injection stroke, wherein the clutchmechanism further comprises an inner rear tube arranged around theclutch fingers inside the torsion spring and attached to the outer reartube at their distal ends, the inner rear tube having a number ofinternal longitudinal splines for engaging the flexed-out clutchfingers.
 25. Auto-injector according to claim 24, characterized in thatthe internal longitudinal splines are arranged in a manner to form aratchet when engaged with the clutch fingers.
 26. Auto-injectoraccording to claim 15, characterized in that a locking mechanism isprovided for locking the needle shroud in its advanced position. 27.Auto-injector according to claim 15, characterized in that at least oneviewing window for inspecting the syringe is provided in the housing.28. Auto-injector according to claim 20, characterized in that the leadnut is provided with at least one pin or with a ball bearing forengaging the external lead screw thread.